allergy and hypersensitivity reactions

Hypersensitivity reactions - the Gell & Coombs classification

antigen binds to Antigen presenting Cell (APC) ⇒ activates T Helper cell ⇒ IL-4 production ⇒ B IgE type ⇒ IgE production

mast cell degranulation due to either:
- IgE from priming event binds antigen complex
  - it appears a protein, neuritin, prevents the over-production of IgE and thus allergies, anaphylaxis, asthma and many auto-immune conditions could be the result of a deficiency of neuritin according to researchers at the Australian National University (ANU) in 2021
- direct degranulation via C3alpha/C5alpha, morphine, codeine;
⇒ immediate granule release (~20 min)
- histamine, etc
- ⇒ H1 effector ⇒ increased permeability; urticaria; asthma;
- ⇒ H2 feedback ⇒ down-regulation
- ⇒ decreased mast cell degranulation
- ⇒ decreased PMNL activity, etc;
- ⇒ activation phospholipase A2 (slow ~8 hrs, inhib. by NSAID/steroids)
- ⇒ PG, thromboxane, SRS-A, leukotriene production;

Ab + Ag (assoc. with or part of a cell/tissue) ⇒ complement activation
- ⇒ lytic action on cell memb. via complement/effector cell products
eg. Goodpasture's disease; Rh isoimmunisation disease of pregnancy; autoimmune haemolyticanaemia;
eg. myasthenia gravis (not lytic though only Ig bind Ach receptors)

Ab-Ag complexes in circulation in ratio 1-2:1 may cause deposition onto cell membranes activating complement
- ⇒ local inflammation including urticaria with joint effusions
eg. serum sickness (such as due to 1-2wks after taking cefaclor)
if Ab»Ag, then v.large complexes which are taken up by phagocytes & hence no serum sickness;

hapten on/in epidermis activates Langerhan's ⇒ LN T cells
- ⇒ local mainly epidermal inflammatory response
  - ⇒ spongiosis/blisters with initially lymphocytic infiltration & later macrophages;
eg. poison oak; nickel;

soluble transient hapten in dermis activates macrophages
- ⇒ dermal response ⇒ papule with monocytic infiltrate & some macrophages;